The field of the invention is lymphokines and fibrosis.
Schistosomiasis is one of the most important helminthic diseases, estimated to afflict 200 million people in the tropics (Walsh et al., 1979). Two of the schistosome species that infect humans (Schistosoma mansoni and S. japonicum) can cause serious morbidity (including portal hypertension and gastrointestinal hemorrhage) as a result of a form of hepatic fibrosis (Cheever et al., 1967). However, only a relatively small subpopulation (3-6%) of infected individuals develop this scarring; the others remain generally healthy (Chen et al., 1988).
Traditional forms of antihelminthic therapy have a number of undesirable side effects, and treatment with the relatively new drug, praziquantel, is very expensive, thus making antihelminthic treatment of all infected individuals impractical. In addition, while early antihelminthic therapy may aid in preventing liver scarring, it has not been established that this is an invariable outcome of treatment (Homeida et al., 1988).
Alternatively, early aggressive treatment of infected individuals with anti-inflammatory or immunosuppressive drugs including methotrexate, cytotoxins and various corticosteriods may aid the prevention of scarring. However, given that these drugs are known to produce a number of relatively severe side effects, treatment of all infected individuals, 94-97% of which would never develop the progressive fibrotic form of the disease, is both undesirable and impractical.
Several other chronic inflammatory diseases, including pulmonary fibrosis, scleroderma/progressive systemic sclerosis, sarcoidosis, sclerosing cholangitis, primary biliary cirrhosis and inflammatory bowel disease also can result in organ dysfunction due to pathological fibrosis. As in schistosomiasis, only a subpopulation of individuals with these diseases develop debilitating organ scarring. Thus, methods are needed that would make it possible to predict which patients will develop the progressive fibrotic forms of these inflammatory diseases so that more aggressive, antifibrotic courses of treatment can be limited to only those individuals who would benefit from these treatments.